Multidrug-resistant strains of many clinically important pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Mycobacterium tuberculosis, and Enterococci strains are becoming a worldwide health problem. There is an urgent need to discover new agents to treat patients infected with multidrug-resistant bacteria. Many thiazolyl peptide antibiotics possess potent antimicrobial activity against Gram-positive bacteria, including multidrug-resistant strains. Novel nocathiacin derivatives and related thiazolyl peptide derivatives, having inhibitory activity at the nanomolar level against Gram-positive bacteria, have been discovered. The nocathiacin derivatives and related thiazolyl peptide derivatives described herein exhibit potent antimicrobial activity against Gram-positive bacteria in vitro, and exhibit in vivo efficacy in a systemic Staph. aureus infection model in animals.
The novel nocathiacin derivatives of this invention are derived from the thiazolyl peptide antibiotic, nocathiacin I or II described by J. E. Leet et al in U.S. Pat. No. 6,218,398, issued Apr. 17, 2001, (corresponding to PCT Appl. WO 00/03722, published Jan. 27, 2000), and nocathiacin IV described by W. Li et al in PCT Appl. WO 02/13834 (published Feb. 21, 2002).
Nocathiacin I has the structure:

Nocathiacin II is identical in structure to Nocathiacin I, except OR2 is H, rather than OH as in Nocathiacin I.
Other nocathiacin derivatives are described in U.S. Pat. No. 6,287,827 granted Sep. 11, 2001; PCT WO 00/14100 published Mar. 16, 2000; and PCT WO 02/14354 published Feb. 21, 2002.
Neither the novel nocathiacin derivatives described here nor their use in treating infectious diseases is known or suggested by prior art.